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Figures & Tables

Fig 1.

Flowchart displaying the composition of the studied group. GD, Graves’ disease; GO, Graves’ orbitopathy.
Flowchart displaying the composition of the studied group. GD, Graves’ disease; GO, Graves’ orbitopathy.

Fig 2.

Boxplots comparing IgG4 serum concentration between GD without orbitopathy, moderate-to-severe GO, and the control group. GD, Graves’ disease; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4.
Boxplots comparing IgG4 serum concentration between GD without orbitopathy, moderate-to-severe GO, and the control group. GD, Graves’ disease; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4.

Fig 3.

The ROC curve of IgG4 as a diagnostic tool for diagnosing moderate-to-severe GO. The optimal cut-off value determined by the highest Youden index was 49 mg/dL. At this cut-off value, the AUC was 0.851 (P < 0.001), negative predictive value was 100%, positive predictive value 48%, sensitivity 100%, and specificity 73%. AUC, area under the curve; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4; ROC, receiver operating characteristic.
The ROC curve of IgG4 as a diagnostic tool for diagnosing moderate-to-severe GO. The optimal cut-off value determined by the highest Youden index was 49 mg/dL. At this cut-off value, the AUC was 0.851 (P < 0.001), negative predictive value was 100%, positive predictive value 48%, sensitivity 100%, and specificity 73%. AUC, area under the curve; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4; ROC, receiver operating characteristic.

Comparison of IgG, IgG4, and other biochemical features between hyperthyroid and euthyroid patients with GD

Hyperthyroid GD (N = 32)Euthyroid GD (N = 28)P-value
IgG4 (mg/dL)33 (23.78; 58.3)52.4 (29.45; 95.6)0.061
Total IgG (g/L)11.72 (10.88; 13.09)10.65 (9.77; 12.34)0.098
TSH (μU/mL)0.01 (0.01; 0.01)1.55 (0.81; 2.25)<0.001
fT3 (pmol/L)25.72 (17.35; 31.95)4.72 (4.44; 5.23)<0.001
fT4 (pmol/L)48.91 (38.08; 79.9)15.14 (13.09; 16.01)<0.001
TRAb (IU/I)13.23 (6.43; 23.31)2.09 (0.9; 3.98)<0.001
TPOAb (IU/mL)246 (59.75; 410.75)63 (27; 147.25)0.004
TgAb (IU/mL)271 (35.25; 525.25)20.5 (10.75; 164)0.006
CRP (mg/dL)1.15 (0.5; 2.53)1.05 (0.48; 2.13)0.953
Moderate-to-severe GO (% of patients)9.3832.140.050

Correlations of selected biochemical, hormonal, anthropometric, and ultrasound parameters with serum IgG4 and IgG levels

IgG4Total IgG
IgG4ρ = 0.072, P = 0.586
Total IgGρ = 0.072, P = 0.586
Age (years)ρ = (−)0.085, P = 0.517R = (−)0.239, P = 0.066
CRPρ = (−)0.084, P = 0.523ρ = (−)0.070, P = 0.594
TSHρ = 0.236, P = 0.070ρ = (−)0.149, P = 0.258
fT3ρ = (−)0.197, P = 0.131ρ = 0.353, P = 0.006
fT4ρ = (−)0.260, P = 0.045ρ = 0.387, P = 0.002
TRAbρ = (−)0.270, P = 0.037ρ = −0.032, P = 0.803
TPOAbρ = 0.052, P = 0.695ρ = 0.130, P = 0.324
TgAbρ = 0.202, P = 0.685ρ = 0.202, P = 0.122
Creatinineρ = 0.117, P = 0.373ρ = 0.062, P = 0.637
ALTρ = (−)0.167, P = 0.202ρ = 0.033, P = 0.800
ASTρ = (−)0.047, P = 0.724ρ = 0.103, P = 0.433
WBCρ = (−)0.0512, P = 0.697R = (−)0.106, P = 0.421
RBCρ = 0.0852, P = 0.517R = 0.219, P = 0.093
Hemoglobinρ = 0.033, P = 0.800R = (−)0.133, P = 0.309
PLTρ = (−)0.033, R = 0.800R = 0.142, P = 0.278
Thyroid volumeρ = (−)0.233, P = 0.087ρ = 0.145, P = 0.290
Intrathyroidal blood flowρ = (−)0.075, P = 0.594ρ = 0.073, P = 0.603
Thyroid echogenicityρ = 0.077, P = 0.578ρ = (−)0.153, P = 0.266
Number of thyroid nodulesρ = (−)0.263, P = 0.054ρ = (−)0.322, P = 0.117

Comparison of clinical, biochemical, and ultrasonographic features between high IgG4 and normal IgG4 GD

GD patients with IgG4 serum concentration within normal range (N = 54)GD patients with high IgG4 serum concentration (N = 6)P-value
IgG4 (mg/dL)33.9 (25.73; 67.8)159.5 (143.78; 174.93)<0.001
Total IgG (g/L)11.25 (10.31; 12.4)11.39 (10.69; 14.58)0.411
Age (years)39.96 ± 13.4438.83 ± 11.840.844
Gender (% of males)14 (25.93%)1 (16.67%)1
TSH (μIU/mL)0.01 (0.01; 1.33)1.54 (0.34; 1.94)0.095
fT3 (pmol/L)10.78 (4.74; 26.2)6.06 (4.93; 6.76)0.498
fT4 (pmol/L)30.16 (15.4; 53.4)15 (13.18; 18.33)0.112
TRAb (IU/I)6.03 (2.56; 16.82)2.68 (1.54; 3.56)0.078
TPOAb (IU/mL)122.5 (31.25; 281)218 (154.5; 280.75)0.538
TgAb (IU/mL)71 (13; 325)246 (84.5; 554.5)0.204
CRP (mg/dL)6.03 (2.56; 16.82)2.68 (1.54; 3.56)0.408
Creatinine (mg/mL)0.57 (0.44; 0.73)0.62 (0.57; 0.73)0.267
ALT (U/I)23.5 (17.25; 32)24.5 (17.25; 28.75)0.970
AST (U/I)21.5 (16; 25)22.5 (20.25; 26.25)0.330
WBC (×103/μL)6.46 ± 1.756.35 ± 2.30.878
RBC (×106/μL)4.71 ± 0.44.76 ± 0.180.802
Hemoglobin (g/mL)13.55 (12.63; 14.38)14.1 (13.6; 14.38)0.810
PLT (×103/μL)4.71 ± 0.44.76 ± 0.180.802
Thyroid volume (cm3)29.82 ± 21.8319.35 ± 15.250.233
Intrathyroidal blood flow1 (0; 2)1 (0.25; 1.75)0.707
Thyroid echogenicity1 (1; 2)1 (1; 1.75)0.792
Presence of any thyroid nodule (% of patients)36.7316.670.653
Presence of multiple (≥3) thyroid nodules (% of patients)18.3700.574
Moderate-to-severe GO (% of patients)14.8166.670.012
Language: English
Submitted on: Mar 21, 2024
Accepted on: Jun 20, 2024
Published on: Jul 20, 2024
Published by: Hirszfeld Institute of Immunology and Experimental Therapy
In partnership with: Paradigm Publishing Services
Publication frequency: 1 times per year

© 2024 Michal Olejarz, Ewelina Szczepanek-Parulska, Aleksandra Krygier, Elzbieta Wrotkowska, Nadia Sawicka-Gutaj, Marek Ruchala, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.